To explore the possibility of an important atypicality dimension within the group of primary, endogenous depression, we have constructed a rating scale for atypical depressive illness. Forty-four NIMH patients were rated, all meeting Research Diagnostic Criteria for primary, major depressive illness. Atypicality in this group was characterized by lack of encapsulated episodes, interpersonal difficulties, evidence of narcissistic character disorder, and high anxiety and somatization. Though atypical patients were younger than typical, they were hospitalized significantly more often. Biologically, they had smaller variance in two measures of norepinephrine metabolism, as well as lower levels of platelet MAO. Typicals were significantly more likely to have an antidepressant response to sleep deprivation than atypicals. Thus, atypicality as a dimension within primary, major depression may have important theoretical and clinical implications.